Abstract

Periodontal disease is a chronic microbial infection of gums and surrounding
tissues. The host response to bacterial infection results in overproduction of
cytokines and other inflammatory markers which has been held responsible
for various systemic conditions like diabetes, respiratory disease, adverse
pregnancy outcomes and cardiovascular events. In recent years few studies
have thrown light on the association of periodontitis with infertility and concluded
that there could be possible association between periodontal disease and
woman’s chance of conception and effectiveness of infertility treatment. The
evaluation of periodontal clinical parameters within IVF programme is a new
field of research with limited information. Furthermore, effect of bacteriospermia
secondary to periodontal disease resulting in decreased sperm motility or count
or increased sperm apoptosis remain to be determined as only few studies
have mentioned about these effects. Nevertheless, the confirmation of real
association of periodontal disease with male and female infertility requires
further prospective randomized trials and interventional studies. There is a need
of coherent approach between gynaecologists and dentists to verify the existing
relation which may establish the background for need of periodontal treatment
upon diagnosis before embarking on infertility treatment.

Introduction

Periodontitis is a chronic inflammatory disorder of gums &
surrounding tissues caused by specific microorganisms resulting
in progressive destruction of the periodontal ligament and alveolar
bone with pocket formation, recession or both. The clinical feature
that distinguishes periodontitis from gingivitis is the presence of
clinically detectable attachment loss. Gingivitis is milder reversible
inflammation of the soft tissues around teeth while periodontitis is
severe form of periodontal disease resulting in the destruction of the
alveolar bone supporting structures & soft tissues [1]. Oral health is
gaining lot of importance in recent times and has been associated
with almost all the disease states of the body i.e. Respiratory,
cardiovascular diabetes and adverse pregnancy outcomes [2-5].
Infertility affects around 15% of the couples worldwide and can be
due to many factors like tubal, ovulatory or male factor. Around
30% of cases of infertility are unexplained. Till date little is known
about the effect of periodontal disease on reproductive function and
evidence to support a link between periodontitis and subfertility is
still emerging. In the last few years focus of researchers has been on
the role of periodontitis in infertility. Whether oral health status plays
any part in subfertility of the partners, was the question in our mind.
With this hypothesis that fertility is compromised in people with
chronic dental diseases, we searched the literature and reviewed the
studies published till now in this article.

Methodology

Various studies published so far were searched and review was
carried out to verify the existing research about the association between periodontal diseases and female infertility, and the biological
rationale for such relation. After a judicious literature investigation,
it is possible to state that there is insufficient evidence to confirm the
association until now. More studies proposing to investigate that
relation are, thus, necessary.

Evidence of effect of periodontal diseases on female
fertility

The term infertility is defined as failure of a woman to conceive
after one year of unprotected intercourse. Regarding the effect of
periodontal disease on the female fertility, it has been interpreted
that gram negative bacteraemia resulting from periodontal inoculous
incites the immune mechanism and triggers the overproduction
of pro-inflammatory markers like tumour necrosis factor alpha
(TNF-a), interferon gamma (IFN-g) and interleukin 1 beta (IL-1b) etc
[6]. This has been strongly supported by various studies identifying
that even subclinical infection significantly affects conception
rate. Significant failure rate in achieving pregnancy despite the
fact that there has been appreciable progress in the knowledge and
techniques to treat infertility has recently raised concern regarding
the role of periodontal disease in infertility [7-10]. The question
arises whether the chronic infection from periodontal disease directly
affects endometrium or influences the effectiveness of hormonal
therapy used to treat infertility or indirectly associated with other
subclinical infections causing infertility [11,12]. The answer to the
above seems to be difficult but the possible mechanisms supported
by available literature may be due to local endometrial effect or other
mechanism which is not clear. Collective evidence so far suggest that
successful treatment of periodontal disease have led to improvement in endothelial and vascular function and reduction in the level of
inflammatory markers.

Endometrial effect of periodontitis is corroborated by several
studies [13-16]. This has been explained in similar fashion to other
inflammatory conditions such as hydrosalpinges, endometritis and
polycystic ovarian syndrome in which it is hypothesized that negative
influence on conception relates in part to an endometrial effect. A
cross-sectional study aimed to explore the relation between time to
conceive and periodontitis by Nwhator, et al. [17] concluded that
there is significant association between periodontal disease and
conception time. He further suggested that women of reproductive
age group should have periodic dental checkup and maintain good
oral hygiene.

The answer to the fundamental question that periodontal
infection not only affect reproductive potential but also alters success
and treatment outcome of infertility has barely been explored [18,19].

Effect of periodontal health on infertility treatment

Haytec, et al. [18] compared the women receiving ovulation
induction drugs either oral or injectable with control group and made
reference regarding the impact of medication (ovulation induction
drugs) on gingival tissues. The findings of the study revealed
significant increase in gingival inflammation in medication group.
There was also statistically significant increase in gingival volume
and bleeding tendency on probing and duration of medication was
.almost three months. Potential mechanism for this is increased
level of estrogen and progesterone by the usage of ovulation
induction drugs. Therefore effective plaque treatment and constant
periodontal monitoring should be considered to minimize the effect
of periodontal infection on the success of infertility treatment [20].
Transient elevation of inflammatory markers have been shown after
periodontal treatment so, it is advisable to wait for few weeks before
seeking fertility intervention [21,22]. Hart reported that magnitude of
negative influence of periodontal disease on time to conceiving was of
the same order as obesity. A large cohort of women who were taking
part in “SMILE study” were followed and analyzed information
on conceiving time and pregnancy outcomes [23,24]. This was the
first report to suggest that periodontal disease may be one of the
modifiable risk factor limiting conception and therefore infertile
couples may consider dental health checkup before embarking on
infertility treatment.

Endometriosis is an important cause of infertility and possible
association between periodontal disease and endometriosis was
investigated by cross-sectional survey over a period of 5 years [10].
Author concluded that women with self-reported endometriosis
had significantly (57%) higher odds of having both gingivitis and
periodontitis relative to not having periodontal disease, compared
with women without self-reported endometriosis, when controlling
for other relevant factors.

The evaluation of periodontal clinical parameters within IVF
programme is a new field of research and this fact was first investigated
by Pavlatou [25]. Sixty women undergoing IVF were recruited in the
study and various indices i.e., Gingival index, bleeding on probing,
plaque levels were recorded for all participants before and after
IVF. It was observed that aggravation of gingival inflammation was found after hormonal administration as IVF programme and poor
periodontal status before IVF was associated with more failures.
Whether this increased gingival inflammation affects the final
fertilization of ova needs further investigation.

Few years later in another investigation by same author regarding
possible effect of periodontal status on effectiveness of IVF concluded
that maternal dental status not only gets affected by hormonal
treatment but also may determine the success of IVF [26,27].

Evidence of effect of periodontal diseases on male fertility

Male factor is responsible for about 40% cases of infertility
and endocrine function or testicular abnormalities are the main
attributable causes. The first study evaluating possible association
of men’s infertility with poor oral health involved 36 men with
bacteriospermia who were resistant to antibiotic therapy [28]. They
were segregated into experimental and control group and after six
months semen analysis of experimental group showed significant
improvement in all semen parameters. This observation of positive
correlation of male factor infertility with periodontal disease is
supported by many studies [17,29,30]. High level of bacteriospermia
and increased inflammatory markers secondary to periodontitis
leading to Oligospermia, inhibiting sperm motility and inducing
sperm apoptosis are the proposed aetiologies for male infertility [10].
A study by Klinger, et al. postulated that periodontal pockets lead to
decreased sperm motility and increase risk of male infertility.

Pitfalls in literature

Most of the studies in literature mention about difficulty in
ruling out all confounders and many are limited by small number
of sample size. In a study by Nwhator, et al. [17] effect of stress and
evaluation of spouse was not considered, which could be a possible
cause of infertility. Author has also acknowledged that prevalence
of other fertility related variables like fibroid, PCOS, obesity and
tubal disease also may have affected the result. Hart, et al. [15] found
positive correlation of periodontal disease with infertility in Non
causcian women only and this only reflects positive correlation
with conceiving time not with infertility. This could be because
of different immunogenicity in different races. A good number of
studies support that people with increased immunogenicity are
more susceptible to periodontal diseases [31-33] and on the other
hand various immunological mechanisms are held responsible for
poor reproductive performance and adverse obstetric outcomes. It is
clear from recent reports that modulation of immunogenicity leads
to increase chance of conception [34,35]. Most of the studies are
observational or cross sectional surveys.

Most of the studies establishing correlation between periodontal
disease and male infertility remain unadjusted for smoking, diabetes,
alcohol and heart disease [17,29,31,36-38]. In a study by Haytec, et
al. [18] although gingival inflammation was significantly increased in
experimental group but this did not determine that whether it was
in healthy or diseased peridontium. So additional prospective studies
taking into account the confounders are required to establish real
association between periodontal disease and infertility.

Periodontal diseases are multifactorial and due to many different
periodontal diseases definitions the comparison among them is still
a challenge [39-45]. Experimental animal model studies may benefit by the ability to control the highest number of variables potentially
affecting the outcomes studied (Table 1).

Table 1: Study Characteristics.

Author/year

Location/study design

Sample Characteristics

Main Variables

Main Results

[17]

Nigeria

Case-control

70 pregnant and 58 non-pregnant -

Periodontal examination: with various indices

1. Time to conceive.(More than one year)

2.Periodontal

parameters

There were greater odds of conception within one year for the subgroup with good oral hygiene.

[43]

Australia

Cross-sectional

Total 1956 women

-516 With periodontal pockets = 4 mm

-1439 Without periodontal disease

1. Prevalence of

periodontal

disease

2. Duration to

conceive

Periodontal disease might affect time to conception but only statistically significant in the non-Caucasian

[7]

Australia

Editorial

N/A

N/A

Women planning for conception should have good oral health and treatment should start early before embarking on infertility treatment.

[28]

Aachen

36 male with bacteriospermia resistant to antibiotic therapy divided in two groups

Various semen parameters

Significant improvement in all semen parameters

[44]

Brazil

Animal

Experimental

Study

Wistar rats

-13 periodontally healthy

control group

-27 induced ligature

periodontitis group

Prematurity

Fetal weight

,inflammatory markers, placenta, cord

Ligature-induced periodontitis did not result in adverse pregnancy outcomes

Infertility was a secondary outcome found in the periodontitis group

[45]

United States

Animal

Experimental

Study

Murines

8 blank control

8 negative control

12 Campylobacter rectus infection

12 Campylobacter rectus and Porphyromonas gingivalis infection

Fecundity

Histologic placental inflammation

Reduced fertility

Fetal resorption

Placental inflammation with necrosis areas

Infertility was a secondary outcome found in the oral infected group

Table 1: Study Characteristics.

Conclusion

Although literature has several reports concluding the association
of periodontal disease with male & female infertility, there are
inconsistencies regarding result of these studies. Collective evidence
suggests that periodontal infection may increase the risk of infertility
because of overproduction of pro-inflammatory markers into the
systemic circulation. Despite the lack of convincing evidence to
confirm real association between two, periodic dental check-up
and management of periodontal disease should be considered in all
women of reproductive age group. We believe that all females seeking
infertility treatment should undergo proper counselling and screening
for periodontal disease. There is a need of coherent approach between
gynaecologist and dentist and further interventional prospective
randomized studies are required to substantiate the correlation
between periodontal infection and infertility.